Abstract Given the elevated mortality of COVID-19 infections in older adults (Wu et al 2020), there is an urgent need to evaluate medicines that may prevent severe disease in these vulnerable patients. Inhibition of targets downstream of target of rapamycin complex 1 (TORC1) was reported to upregulate pan-antiviral gene expression and protect mice from a viral respiratory tract infection (RTI) (York AG et al. 2015). Importantly, RTB101 was also observed to upregulate interferon-stimulated pan-antiviral gene expression, decrease the levels of inflammatory cytokines in serum, and decrease the incidence and severity of viral respiratory tract infections including coronavirus infections when given as prophylaxis during winter cold and flu season to older adults (Mannick et al. 2018, Mannick et al., 2019). Therefore we hypothesize that RTB101 will decrease the incidence and severity of COVID-19 when given as prophylaxis to older adults. Before undertaking a large well-powered trial for this indication, we propose to undertake a pilot study to determine the feasibility of recruiting, consenting, screening and randomizing quarantined outpatient populations of older adults who are predicted to be at increased risk of developing COVID-19 (Specific Aim 1), assess whether COVID-19 symptoms can be tracked using an eDiary in older adults (Specific Aim 2), and obtain preliminary data on the incidence and severity of COVID-19 in subjects treated with RTB101 as compared to placebo (Specific Aim 3). The data generated in the trial will be used to help optimize the study design of a larger adequately powered study to determine if RTB101 is effective as COVID-19 prophylaxis in the older adults. References 1. Mannick, J. B., Morris M, Hockey HP, Roma G, Beibel M, Kulmatycki K et al. (2018) TORC1 inhibition enhances immune function and reduces infections in the elderly. Sci Transl Med 10, doi:10.1126/scitranslmed.aaq1564. 2. Mannick et al, (abstract) IDWeek, 2019. 3. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Feb 24. 4. York AG, Williams KJ, Argus JP, Zhou QD, Brar G, et al. (2015) Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling. Cell. 163(7):1716-29.